Protecting fabrics with a bacteriotoxic-fungitoxic application of alpha,omega-alkylenebis (triphenylphosphonium salt)



United States Patent 2 Claims ABSTRACT OF THE DISCLOSURE The invention is directed to a method for protecting fabrics from bacterial and fungal attack comprising: applying a bacteriotoxic-fungitoxic amount of a compound of the formula:

wherein X represents an anion and Where n is an integer of from 6 to 14, to said fabric to be protected from bacterial and fungal attack.

The instant application is a divisional of copending application, Serial No. 481,941, filed on August 23, 1965, now US. Patent 3,364,107.

The instant invention relates to novel antimicrobial, fungicidal and algicidal compositions and to methods for their use. More particularly, it relates to such biocidal compositions containing as the active component thereof an a,w-alkylenebis[triphenylphosphonium salt] and to methods for controlling the growth of such diverse organisms, as bacterta, fungi and algae.

Many antimicrobial, fungicidal and algicidal compositions are presently known. However, few such compositions exhibit broad spectrum activity for demanding use under an ever widening variety of conditions. For instance, many algicides for use in treatment of tower cooling waters as well as pool waters are not effective over a protracted time period due to the presence of oxidants, such as chlorine, which cause their ready degradation. In swimming pools and in industrial waters used in cooling towers for airconditioning, algae are a considerable problem. They produce mats of slime which restrict the flow of water through heat exchangers, serve as food for bacteria, cause slippery, hazardous conditions in pools and are unsightly. Chlorine is normally added to swimming pools in amounts ranging from about 0.1 to about 0.5 part per million and often to cooling waters for bacterial control but many algae species are chlorine resistant to the low levels of chlorine used. Higher levels of chlorine are not usable because of eye and mucous membrane irritation in pools and corrosion inducing properties in cooling water systems. Where higher levels of chlorine are used, known algicides are generally degraded and destroyed.

Biocidal compositions to be useful should be effective against an encountered organism which is to be controlled. In this connection, the compositions should be (a) safe to handle and (b) stable under those conditions prevailing at the point of contact or application. It is therefore,

a principal object of the invention to provide such compositions and to provide methods for their use.

In accordance with the present invention, it has been surprisingly found that compositions containing as an active ingredient thereof the compound of the general formula:

wherein n is an integer from 6 to 14 and X represents an anion, such as, for instance, perchlorate, nitrate, sulfate, chloride, bromide, iodide, ROSO ROCO-, or RS0 where each R is alkyl or aryl, are highly effective under a wide variety of conditions. Unexpectedly, the high level of activity of compositions of the present invention against a large variety of pathogenic organisms coupled with good water solubility, low phytotoxicity, good stability to heat, light, chemical oxidants, fabric softener and detergents cogently points up the markedly enhanced disinfectant and sanitizing properties of the aforementioned compositions.

In general, the active algicidal, fungicidal and antimicrobial compounds employed in the process of the invention are prepared in a straightforward manner by heating an alcoholic solution containing one mole of an appropriate a,w-dihaloalkane with about two or more moles of triphenyl phosphine. Resultant product is then regovered as by filtration or by precipitation with ethyl et er.

In the preparation of the identified compositions, either a suitable alkane dialkyl sulfonate ester or an alkane diarylsulfonate ester can be substituted for the ,w-dihaloalkane reactant to yield the corresponding alkyl sulfonate or aryl sulfonate salts, respectively, of the identified compositions. Other salts, such as acetates, nitrates, sulfates or perchlorates, can be prepared from the resultant dihalide, for example, by well-known exchange reactions.

Illustrative a,w-alkylenebis[triphenylphonium contemplated by the invention are:

salts] 1,8-octamethylenebis [triphenylphosphonium chloride] 1, 16-hexadecamethylenebis [triphenylphosphonium bromide];

1, 16-hexadecam-ethylenebis [triphenylphosphonium chloride];

1,1Z-dodecamethylenebis[triphenylphosphonium bromide];

1,8-octamethylenebis[triphenylphosphonium ethyl sulfate];

1, 12-dodecamethylenebis [triphenylphosphonium propyl sulfate];

1, l6-hexadecamethylenebis [triphenylphosphonium acetate];

1, 12-dodecamethylenebis [triphenylphosphonium toluene sulfonate];

1,8-octamethylenebis[triphenylphosphonium nitrate];

1,10-decamethylenebis[triphenylphosphonium nitrate] 1, l0-decamethylenebis [triphenylphosphonium perchlorate] 1,8-octamethylenebis [triphenylphosphonium perchlorate] 1,10-decamethylenebis[triphenylphosphonium sulfate] and 1, 8-octamethylenebis [triphenylphosphonium sulfate] Advantageously, a wide range of growth inhibiting amounts of salt herein contemplated may be admixed with an inert carrier applied to an area to be treated. Thus, in treating swimming pool water, a small, but effective, amount from 1 to 100 parts per million (p.p.m.) of the The contents of each tube are thoroughly mixed and poured into petri dishes to harden. Aqueous suspensions of the test cultures of fungi are then streaked upon the surface of the agar and permitted to incubate for 48 or 96 hours. After incubation, all plates are examined and the salt can be added to the water to be treated either as such 5 results recorded. Controls are prepared in the same manner or diluted with a major amount of water to inhibit algae as stated above with the exception that the agar employed growth. Minor amounts of the salts may also be inis free of test compound. Cultures of each test organism corporated into major amounts of other diverse extenders, are also streaked on the control agar surface and are such as starch, natural gums, agar, commercially availfound to proliferate profusely. able synthetic detergents of the anionic or non-ionic types. Results of the tests are recorded in Table I below where- For use in the latter detergent extender, as much as 300 in the lowest concentration, in parts per million, of test ppm, or more, can be tolerated to inhibit microbial compound found to produce 100% control of the test growth. organism is presented.

TABLE I Compound P.p.m Organism 250 Candida albt'cans. 62 Saccharomyces ccrevisiae. 62 M ucor ramannianus. F] 8 Harmodendrum cladosporoidcs.

PCH2(CH2)3CH2P -2Br 31 Trtchophytan mentagrophytes. is L s 4 Microsparum gypsaum.

8 Pcnict'llt'um digitatum. 2 Memnoniclla echinata. 4 Chactomz'um globosum. 5O Aspcrgillus fumigatus.

The inveniton will be further illustrated in conjunction Substituting for the test compound in Table 1, 1,8- with the following examples which are to be taken as octamethylenebis[triphenylphosphonium bromide], subillustrative only and not by way of limitation. All parts stantially the same results as reported in Table I are are by weight unless otherwise noted. noted.

A typical preparation of the illustrative biocidal com- Example 3 pounds 15 Presented below 35 Activity of the compounds of the instant invention in Example 1.Preparation of 1,10-decamethylenebis- Foljltroning both gram'positive and gram'nFgalive bacteria [triphenylphosphonium bromide] 18 illustrated by the following tests wherein graded levels of 1,10-decamethylenebrs[trlphenylphosphomum bro- A mixture of 110 parts of triphenyl hos hine, 60 mide] are dissolved or suspended in sterile hot trypticaseparts of 1,10-dibromodecane, and 100 parts (by volume) 40 Oy g Casein P P IIe, 0.5% s y p p 05% of n-butyl alcohol are refluxed in a suitable reaction vessel sodium chloride, agar) and poured n petri dishes for 18 hours, then cooled to permit the addition of diethyl to harden. Suspensions of bacterial organisms are ether. From thi mixture a tacky product re i itated, i streaked on the agar surfaces and incubated for 48 hours, eparated from the ether and dissolved i a mi i then examined for bacterial proliferation and the results amount of n-butyl alcohol and again reprecipitated from recorded. These results are provided in Table II and are diethyl ether. The precipitate is dissolved in 250 cc. of reported as t lowest concentration of test compound boiling n-butyl alcohol, then cooled and treated with dihich p oduces 100% bacterial control. ethyl ether. The purified product had a melting point of Activity of the Compounds of the invention against 232 C. to 234 C. anaerobic bacteria is determined by a broth dilution E l 2 50 method of assay. In this method, graded levels of 1,10-

decamethylene-bis[triphenylphosphonium bromide] in Antifungal activity of the compounds of the instant one milliliter of solution are added to 9 milliliters of thioinvention is demonstrated in the following tests wherein glycollate medium. The solutions are inoculated with the accurately weighed amounts of 1,10-decamethylenebisorganism Clostridium sporo'genes and incubated for 48 [triphenylphosphonium bromide] are placed in test tubes hours at 37 C. At the end of the incubation period, the and dissolved or suspended in predetermined quantities of solutions are examined. Those found to be clear with no sterile, hot fluid asparagine agar (meat extract, 2.0 grams; growth are read as active, those which are cloudy or have asparagine, 0.5 gram; dibasic potassium phosphate, 0.5 a characteristic odor are read as inactive. As in Example gram; agar, 20.0 grams; water, q.s. to 1000 milliliters 1, results are reported as the lowest concentration of comwith no pH adjustment) to provide known concentration 30 pound found to produce control of the test ortest material in the agar. ganism in Table II below.

TABLE II Compound Organism Gram-negative.

. Anaerobic.

Example 4 Laundry washing tests are carried out in screw-capped, 8-ounce wide-mouth jars with agitation provided by a reciprocating machine operating at 180 cycles per minute. To each jar is added 20 milliliters of hot (60 C.), 0.25% w./v. acqueous non-germicidal, anionic synthetic detergent, that is a built, alkyl aryl sodium sulfonate all purpose, granular detergent solution, and 3 or 4 glass beads. The jars and contents are then sterilized for minutes at 121 C., cooled, placed in a Water bath at 60 C. and 1 milliliter of an acetone solution containing 0.1 milligram 1,10 decamethylenebis[triphenylphosphonium bromide] is added. (The germicide concentration is thus 5 p.p.m. with respect to the wash water, or expressed in terms of the weight of detergent, the concentration is 0.2%). Twenty l-inch diameter circular discs of unbleached cotton fabric, weighing about 1.0 gram, are added, the jars briefly swirled to distribute the circles, and transferred to the reciprocating shaker. Jars are shaken for 10 minutes at the end of which time the wash Water is next decanted and replaced with 100 milliliters sterile water at room temperature. The simulated rinse cycle lasts one minute. The rinse water is decanted and the circles transferred to sterile wire screens and dried for 30 minutes at 50 C. to 55 C.

Cotton fabrics so laundered are imparted with an antibacterial finish as evidenced by their failure to support growth when inoculated with a suspension of a viable culture of Staphylococcus auresus or Brevibacterium ammoniagenes implanted on the surface of a solidified nu trient agar and incubated 48 hours at 37 C.

Similar results are obtained utilizing 1,12-dodecamethylenebis[triphenylphosphonium chloride] in lieu of 1,10- decamethylenebis [triphenylphosphonium bromide] Control fabric similarly laundered but in the absence of a "germicide supported luxuriant growth of Sta phylococcus aureus and Brevibacterium' ammon-iagenes.

Example 5 Cotton cloth circles are laundered as described in Example 4 above. The cloth to liquor ratio is maintained at 1:20, respectively, and germicide concentration at 5 p.p.m. with respect to wash water. However, 0.1 milliliter of bleach solution, diluted percent with water, is added after the germicide addition, but prior to adding the cotton circles. The laundry bath now contains about 200 p.p.m. of available chlorine. Cotton circles are then added, subjected to the wash, rinse, and drying steps as previously described, and inoculated with a suspension of viable Staphylococcus aureus. Cotton fabric so treated and in cubated 2 days at 37 C. on nutrient agar failed to support bacterial growth. In contradistinction, luxurious growth of Staphylococcus aureus is obtained when control swatches washed in the detergent alone or in detergent containing 5 p.p.m. of 3,4,4'-trich1orocarbanilide are similarly incubated on nutrient agar.

Example 6 Cotton swatches are washed as described in Example 5 in the germicide-detergent system with about 200 p.p.m. available chlorine present. Samples are dried at 50 C. to 55 C. for minutes and then autoclaved for 15 minutes at 121 C. Cotton swatches so treated effectively suppressed the growth of Staphylococcus aureus, whereas control fabric washed in the absence of germicide supported growth of Staphylococcus aureus at a density of 3000 to 4000 colonies per square inch.

Example 7 Cotton circles washed and dried as described in Example 5 are subjected to ultra-violet irradiation for-2 hours at a distance of one meter from the lamp. (This exposure is equivalent to 8 hours of sunlight.) Samples so treated failed to support growth of Staphylococcus aureus, whereas control fabrics laundered in non-germicidal detergent and similarly exposed to ultra-violet irradiation supported luxurious growth.

Example 8 Cotton swatches are laundered as described in Ex ample 5 except that the final germicide concentration is now 1.67 p.p.m. with respect to the wash water (0.067% on the detergent weight) instead of 5 p.p.m. The rinsed and dried samples are inoculated with a suspension of a viable culture of Brevibacterium ammoniagenes, implanted on nutrient agar, and incubated for 2 days at 30 C. No bacterial growth is evident on samples so treated, whereas control swatches laundered in non-germicidal detergent with 200 p.p.m. available chlorine supported the growth of more than 2000* colonies per square inch.

Example 9.Antibacterial activity TABLE III Minimum Inhibitors Concentration Test micro-organism (in meg/ml.) of

decamethylenebisflriphenyl-phosphonium bromide] Bordetella bronchiscplica 25 Escherichia coli 1 1 1 25 Salmonella gallmarum 125 Salmonella typh0sa 5 Staphylococcus aurcus.

Example 10.Antifungal activity against plant pathogens The activity of the compounds of the instant invention against the organisms Mom'linia fructicola, the pathogen that incites American brown rot of stone fruit, Stcmphylium sarcinacforae, the pathogen responsible for leafspot of several legumes and Aspcrgillus niger, a saprophyte which degrades textiles, fabrics, leather and stored fruits and vegetables, is demonstrated by the following test wherein sufiicient amounts of 1,10-decamethylenebis[triphenylphosphonium bromide] are dissolved or suspended in water to provide dilutions of p.p.m., 10 p.p.m. and 1 p.p.m. of test compound in solution when 0.4 ml. of solution is added to 3.6 ml. of a spore suspension of the test organism.

Separate spore suspensions of the above-identified pathogens are prepared from 7 to 10-day cultures of the organisms grown on potato-dextrose agar slants. The spores are washed from the agar slants with distilled Water and are adjusted to a concentration of approximately 50,000 spores per cc. of water. Two ml. of orange juice is added per liter of spore suspension to facilitate germination. To outiclear vials, 0.4 ml. of solution of test compound is added along with 3.6 ml. of spore suspension. The vials are then placed on a tumbler and the tumbler rotated to assure contact of chemical and organism. At the end of a 24-hour exposure period, the suspensions are examined microscopically to determine if germination has occurred. The results of the above test are recorded in Table IV below.

TABLE IV Slcmphylium .Monilina frncticola sarcinacforae Aspcrgillus mger 100 10 1 100 10 1 100 10 l p.p.m. ppm. ppm. ppm. p.p.m. ppm. p.p.1n. ppm. p.p.m.

Percent Kill 100 95 100 100 95 100 100 0 EXAMPLE l1.Alga inhibition TABLE V Amount of 'Ioxicant Algae in p.p.rn.

Black algae (a chlorine resistant bluegreen)... 1. 5 Ankistrodesmus species (green) 0. 8 Clamydomonas species (green) 0. 8

Similar results are obtained employing 1,16-hexadecamethylenebis[triphenylphosphonium chloride] in lieu of the toxicant used in this example.

EXAMPLE 12 Cotton fabrics are laundered following the procedure of Example 4, except that they are subjected to a total of three rinses and dried. It is noted that the so-laundered fabrics fail to support growth of S. anreous, whereas the control fabrics similarly laundered without any germicidal additive support luxurious growth. A durable antibacterial finish is thus imparted to the laundered fabrics 'by the exemplified 'biocidal compounds. So-treated fabrics are particularly well suited for use under conditions requiring a substantial degree of bacterial control.

It is believed that the durability of the fabrics finish is due to the substantivity of the compositions defined above.

Example 13 This example demonstrates the effect of 1,10-decamethylenebis[triphenylphosphonium bromide) in controlling the organism, Pityrosporum ovale, which is readily isolated from the human scalp.

Activity against Pityrosporum ovale is determined by an agar dilution method in which graded levels of 1,10- decamethylenebis[triphenylphosphonium bromide] are dissolved in molten Emmons agar (1% Neopeptone, 4% dextrose and 2% agar) and poured into petri dishes to harden. A suspension of P. ovale in sterile corn oil is streaked over the surface of the hardened plates and incubated for 72 hours at 30 C. At the end of this time, plates are examined. It is noted that as little as parts per million of the compound suppress the growth of the aforementioned organism.

We claim:

1. A method of protecting fabrics from bacterial and fungal attack comprising: applying a bacteriotoxic-fungitoxic amount of a compound of the formula:

wherein X represents an anion and where n is an integer of from 6 to 14, to said fabric to be protected from bacterial and fungal attack.

2- The method according to claim 1 wherein the compound is: 1,IO-decamethylenebis[triphenylphosphonium chloride].

References Cited UNITED STATES PATENTS 3,364,107 1/1968 Berenson et a] 167-30 FOREIGN PATENTS 1,145,292 3/1963 Germany.

OTHER REFERENCES Chem. Abstracts 41: 5572h-5573a (1947). Chem. Abstracts 47: 101230 (1953). Chem. Abstracts 47: 814f (1953).

LEWIS GOTTS, Primary Examiner.

S. K. ROSE, Assistant Examiner.

US. Cl. X.R.

UNITED STATES PATENT OFFICE CERTIFICATE 0F CORRECTION Patent No. 3,432,341 March 11, 1969 Herman Berenson et a1.

It is certified that error appears in the above identified patent and that said Letters Patent are hereby corrected as shown below:

Column 8, line 34, "chloride" should read bromide Signed and sealed this 10th day of November 1970.

(SEAL) Attest:

Edward M. Fletcher, Jr. J

Attesting Officer Commissioner of Patents 

